1. Field of the Invention
The invention relates to a plasma desorption mass spectrometer source. In particular, the invention relates to a plasma desorption mass spectrometer source which contains a pulsed neutron generator to provide an appropriate neutron flux in the direction of a fissionable material producing a pulsed source of heavy ions in order to desorb and ionize large molecules from a material for mass analysis.
2. Description of the Related Art
Accurate determination of molecular weights of biomolecules, such as proteins, is very important in biochemistry and industrial polymer applications as an analytical tool for molecular characterization. The molecular weight is a useful parameter, since it is indicative of the size of a biomolecule and gives an approximation of the number and type of subunits constituting the biomolecule. Of particular importance is the analysis of special proteins used in recombinant DNA research, where the paramount criteria of identity from one protein to another protein is the molecular weight of each protein.
The molecular weight of proteins ranges from 10,000 atomic mass units (amu) to over 500,000 amu. Mass spectrometry is one method used for providing an accurate determination of weights of biomolecules involving large masses. However, conventional mass spectrometers are only useful for measuring molecular weights up to about 25,000 amu.
Mass spectrometry involves three distinct functions: sample ionization, mass analysis and ion detection. FIG. 1 illustrates the high-level structural features of a mass spectrometer, whereby an ion beam 10-1 is provided by an ion source 20-1. The ion beam then passes through a mass analyzer 30-1, which separates the ions based on their charge-to-mass ratios. Such a mass analyzer 30-1 may be of the quadrupole type, magnetic sector type, or time of flight (TOF) type. Both the quadrupole and magnetic sector mass analyzer systems have inherent limitations, however, due to the requirements of larger mass analyzer size for measuring larger ion masses. TOF mass analyzers allow for high molecular mass range, high ion transmission, and have the ability to record ions of different mass simultaneously. Therefore, TOF mass analyzers are preferred devices for analyzing large mass biomolecules. After passing through the TOF mass analyzer 30-1, the ion beam 10-1 arrives at the ion detector 40-1. For TOF spectrometers, the time that an ion arrives at the detector ion 40-1 serves as an indication of the mass of the ion.
Based on improvements in each of the three distinct functions of a mass spectrometer, accurate results can be achieved for measurements of biomolecules of masses below 10,000 amu, and reasonably effective measurements have been performed using Plasma Desorption Mass Spectrometry (PDMS), Matrix Assisted Laser Desorption Mass Spectrometry (MALDI), and Electro-Spray Mass Spectrometry (ESMS), for proteins as large as 25,000 amu. However, at present, both MALDI and ESMS are experiencing technical evolutions to allow for the detection of ions in the mass range of 25,000-500,000 amu.
The original method used in mass spectrometry for detecting heavy molecules utilized primary ions from a radioactive source that traveled at high velocities and which subsequently impacted on a thin film of a sample of interest. This impact then caused a subsequent ejection, or desorption, of secondary ions from that thin film. The term "desorption" means the removal of ions from a surface. These secondary ions were subsequently mass differentiated and detected. PDMS is the original large molecule detecting mass spectrometry technique. A general background of this technology is given by Robert Cotter, in Plasma Desorption Mass Spectrometry: Coming of Age, in Analytical Chemistry, Vol. 60, No. 13, Jul. 1, 1988. A block diagram of a plasma desorption mass spectrometer is shown in FIG. 2. The typical ionization source that is utilized is a 10-.mu.Ci sample of .sup.252 Cf (californium), which is held between two thin sheets of nickel foil. The ionization source is held at the same electrical potential (around 20 kV) as the sample to be analyzed. .sup.252 Cf is used as the source since it has a high probability for spontaneous fission.
.sup.252 Cf decays with a half-life of 2.65 years, of which 97% is decayed as alpha particles and 3% is decayed by spontaneous fission. That is, 3% is decayed as two charged fragments simultaneously emitted in opposite directions, 180 degrees apart from each other. Typically, such a decay involves .sup.106 Tc and .sup.142 Ba, with a total energy of about 200 million electron volts (MeV) and with a total mass of about 200 amu.
At the start of each timing cycle, one of the fission fragments hits a start detector 10-2, which is constructed as a grounded foil that emits secondary electrons collected by a dual channel plate detector 20-2. The output pulse from the detector 20-2 is amplified by amplifier 30-2, passed through a constant fraction discriminator 40-2, and recorded as the start pulse by a time-to-digital converter 50-2. The detector foil 10-2 and the discriminator 40-2 are designed to distinguish fission fragments from lower energy alpha particles, which emit about 6.1 MeV of energy per alpha particle. Discriminator 40-2 only provides an output for energies above the alpha particle energy and is thus responsive selectively to the fission fragments.
At the same time that the first fission fragment impinges the detector foil 10-2, the second fission fragment penetrates sample stage 60-2 (typically made of aluminum) on which sample 70-2 has been deposited on the reverse side thereof.
As a result of their masses and high velocities, the fission fragments emitted from the .sup.252 Cf source are able to deposit large amounts of energy as they impinge on the sample 70-2 on the foil 60-2, allowing for the desorption of high molecular weight species from the sample 70-2. Typically, from 1 to 10 high molecular weight secondary ions are desorbed from the sample 70-2 and accelerated toward a grid 80-2 held at ground potential, where the secondary ions enter a long (15 cm to 3 m) drift region 90-2 with velocities inversely proportional to the square root of their masses. The amount of time needed to travel through the drift region 90-2 is a function of the mass of each particle desorbed from the sample 70-2. These particles are then detected by a detector 100-2; the detector output signals are amplified by an amplifier 110-2, and passed through a constant fraction discriminator 120-2. The output signal from the discriminator is fed to the time-to-digital converter 50-2. The data from the first and second fission fragments are then sent to a processor, such as a computer 130-2, which determines a mass spectrum based on this data.
As noted above, a californium source produces heavy ions, but it does so in a not-very-predictable manner. Another limitation of using the californium source is the low yield of molecular ions. Still another problem with using the californium source is that, since the alpha particles that are emitted are of much lower momentum than the particles emitted by spontaneous fission, the alpha particles greatly increase the number of fragmented ions, and since there is no time correlation for the alpha particle-initiated events, the signal-to-noise ratio levels are markedly decreased. All of these problems contribute to long acquisition times and decreased molecular ion sensitivity.
Therefore, it is desired to find a better source for use in a plasma desorption mass spectrometer, and especially a source useful in measuring molecular weights greater than 25,000 amu.